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February 11, 1998

Potential Chromosome 12 Locus for Late-Onset Familial Alzheimer Disease—Reply

Author Affiliations

Margaret A.WinkerMD, Senior EditorIndividualAuthorPhil B.FontanarosaMD, Senior EditorIndividualAuthor

JAMA. 1998;279(6):433. doi:10-1001/pubs.JAMA-ISSN-0098-7484-279-6-jac81007

In Reply.— The results of our complete genomic screen suggested the location of a potential new locus on chromosome 12 for late-onset AD. The chromosome 12 results were strongest in large, extended, multigenerational AD families (tier 1 in our article) that had little influence from the APOE ∊4 allele (ie, 1 or more affected family members were APOE−X/X, where X is the APOE ∊3 allele or APOE ∊2 allele). While our pedigree structures are similar to, but not as extensive as, the family described by Dr Martin and colleagues, their family is different in that it is strongly influenced by the APOE ∊4 allele, and virtually every affected individual has, or can be inferred to have, at least 1 APOE ∊4 allele.1 Thus, it is likely that the genetic effect on AD in their family is primarily from the APOE ∊4 allele. Considering that the effect in our tier 1 families was independent of the APOE ∊4 allele, the results described by Martin and colleagues are in accord with our findings.

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